Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC-MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: ß = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: ß = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (ß = 0.177, p = 0.011) or NR1I2-rs6785049 (ß = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p < 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.

New method of internal fixation in laparoscopic Tenckhoff catheter placement.

BACKGROUND: Despite obvious advantages of peritoneal dialysis (PD), mechanical complications are responsible for the failure of PD at early stage. Suture fixation in laparoscopic PD catheter method could reduce mechanical complications. In our study, a simple method to fix PD catheter was developed. METHODS: Tenckhoff catheter placement was performed in 49 consecutive patients. In the technique, only two trocars were used. With the help of syringe needle and forceps, a loop of silk was prepared at the abdominal wall. The PD catheter was thread through the loop. The silk ligature was tied subcutaneously keeping the catheter suspended from the abdominal wall. Primary outcomes were catheter-related complications. Secondary outcomes were 6-month catheter survival rates and death within 30 days. Data were analyzed retrospectively. RESULTS: The average operation time was 49.7 ± 15.8 min. Minimum follow-up time was 6 months. No catheter displacement or hernia was detected. One patient had omental wrapping after silk suture rupture, 2 patients had outflow obstruction, and 3 patients had leakage. No one died within 30 days postoperatively. Catheter survival was 95.8% at 6 months. CONCLUSIONS: The method we described greatly reduced the risk of catheter displacement and omental wrap. Also, the required instrument and laparoscopic skill were simple.

Roxadustat on anti-erythropoietin antibody-related pure red cell aplasia in the patient with end-stage renal disease.

Anti-erythropoietin antibody-related pure red cell aplasia (anti-EPO PRCA) is a severe complication in patients who receive erythropoiesis-stimulating agents for nephrogenic anemia. The standard therapy is withdrawl of EPO and immunosuppression. Here, we present successful treatment of anti-EPO PRCA with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor. A 39-year-old woman with end-stage renal disease received recombinant human erythropoietin (rhEPO) subcutaneously. Unfortunately, she developed anti-EPO PRCA and her hemoglobin dropped continuously, whereas she rejected immunosuppressive therapy. The patient failed to achieve spontaneous hematologic recovery with cessation of rhEPO alone, and she became transfusion dependent. Thus, she accepted our advice to try roxadustat for nephrogenic anemia. Surprisingly, after starting roxadustat treatment, her reticulocyte and hemoglobin improved gradually. Four months later, the bone marrow aspiration smear demonstrated a return to normal in erythroid cells. Besides, her anti-erythropoietin antibody converted to negative. All in all, this case reveals the potential effect of roxadustat on anti-EPO PRCA.

Atypical hemolytic uremic syndrome with C3 mutation: A case report and literature review.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Uncontrolled activation of the complement system induced by single or combined complement gene mutations is one of the mechanisms leading to the pathogenesis of aHUS. CASE PRESENTATION: We report a case of a 26-year-old female with a C3 heterozygous gene mutation (p.Asn153Asn). The patient was found to have low complement H factor (CFH) but normal levels of anti-CFH autoantibody. She was treated primarily with plasma exchange and plasma infusion. The patient did not relapse during a 1-year follow-up. CONCLUSION: This is the first case of a novel C3 mutation (p.Asn153Asn) in a patient with aHUS. Further studies are needed to confirm the association between this mutation and the CFH level.

Baicalein protects renal tubular epithelial cells againsthypoxia-reoxygenation injury.

BACKGROUND: To investigate the protective effects and mechanism of baicalein (BAI), a naturally occurring flavonoid, against hypoxia-reoxygenation (HR) injury in renal tubular epithelial cells (HK-2). METHODS: Cultured human renal proximal tubular cell line HK-2 was exposed to 24 h of hypoxia (5% CO2, 1% O2, and 94% N2), followed by 12 h of reoxygenation (5% CO2, 21% O2, and 74% N2). HK-2 cells were divided into three groups: control, HR, and HR-BAI (0.3 µg/ml). Reactive oxygen species (ROS) were measured and cell apoptosis was analyzed by flow cytometry and morphology. ELISAs were performed to determine the levels of IL-1, intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1). IL-1ß, ICAM-1, and MCP-1 mRNA levels were determined by real-time quantitative PCR. RESULTS: HK-2 cells that underwent HR exhibited increases in IL-1ß expression by 0.94%, ROS by 0.59%, ICAM-1 expression by 0.8%, and MCP-1 expression by 1.2%. Moreover, HK-2 cell apoptosis was increased after HR (p < .05). Compared with the HR group, BAI treatment reduced the elevation of oxidative stress (ROS) by 0.76%, as well as HR-mediated induction of IL-1ß and apoptosis of HK2 cells. Protein and mRNA levels of ICAM-1 and MCP-1 were also reduced. CONCLUSIONS: BAI protects renal tubular epithelial cells from HR injury by reducing inflammatory cytokine expression and oxidative stress.

Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro through the upregulation of AQP7 expression by the PI3K signaling pathway.

BACKGROUND: Adipocyte-secreted apelin contributes to decreased adiposity and to improved insulin resistance, but the mechanisms remain unknown. The present study aimed to assess if apelin-13 is an upstream signal regulation factor of aquaporin 7 (AQP7), a water-glycerol transporter present in the plasma membrane of adipocytes that plays a key role in the regulation of lipid accumulation. MATERIAL/METHODS: 3T3-L1 pre-adipocytes were induced to fully differentiated adipocytes; hypertrophic adipocytes were then induced using palmitate. The effects of apelin-13 on AQP7 expression in hypertrophic adipocytes were investigated before and after treatment with LY249002, a PI3K inhibitor. Accumulation of cytoplasmic triglycerides (TG) in hypertrophic adipocytes was also determined. RESULTS: We found that 0.1 mM of palmitate induced a model of hypertrophic adipocytes with a lower AQP7 expression (0.26±0.07 vs. 0.46±0.04, P<0.05). Apelin-13 100 nM or 1000 nM upregulated AQP7 mRNA expression (100 nM: 0.54±0.06 and 1000 nM: 0.58±0.09 vs. control: 0.33±0.04, both P<0.05), and decreased accumulation of cytoplasmic triglycerides in hypertrophic adipocytes. Pretreatment using 10 µM LY294002 prevented the increase in AQP7 expression observed when using apelin-13 alone (apelin-13 + LY49002: 0.38±0.03 vs. apelin-13: 0.54±0.06, P<0.05), as well as the decreased cytoplasmic TG accumulation (apelin-13 + LY294002: 3.79±0.04 µM per µg/ml vs. apelin-13: 3.32±0.08 µM per µg/ml, P<0.05). CONCLUSIONS: Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro, possibly through the upregulation of AQP7 expression by the PI3K signaling pathway. Treatment using apelin-13 and AQP modulators might represent novel treatment strategies against obesity and its related complications.

Poly[[µ(2)-1,3-bis-(imidazol-1-ylmeth-yl)benzene][µ(2)-2,2'-dihy-droxy-1,1'-methyl-enebis(naphthalene-3-carboxyl-ato)]zinc].

In the title compound, [Zn(C(23)H(14)O(6))(C(14)H(14)N(4))](n), the Zn(II) ion is four-coordinated in a distorted tetra-hedral geometry. The 1,3-bis-(imidazol-1-ylmeth-yl)benzene and 2,2'-dihy-droxy-1,1'-methyl-enebis(naphthalene-3-carboxy-l-ate) ligands con-nect the Zn(II) ions alternately in different directions, forming a layered structure parallel to the ac plane. Topological analysis reveals that the whole structure is a (4,4) network. The layers are further assembled into a three-dimensional supra-molecular structure via C-H⋯O and C-H⋯π inter-actions.

Poly[[(1,10-phenanthroline){µ(3)-2,2',2''-[1,3,5-triazine-2,4,6-triyltris(sulfane-diyl)]triacetato}-cadmium] 0.42-hydrate].

The asymmetric unit of the title complex, {[Cd(C(9)H(7)N(3)O(6)S(3))(C(12)H(8)N(2))]·0.42H(2)O}(n), contains a Cd(II) atom, one doubly deprotonated 2,2',2''-[1,3,5-triazine-2,4,6-triyltris(sulfanediyl)]triacetic acid ligand (HTTTA(2-)), a 1,10-phenanthroline (phen) ligand and a fractionally occupied water mol-ecule [site occupancy = 0.421 (15)]. The Cd(II) atom is six-coordinated within a distorted octa-hedral coordination geometry. Six coordination arises from four O atoms derived from three different HTTTA(2-) ligands, and two N atoms of the chelating phen mol-ecule. The incompletely deprotonated triazine ligand adopts a µ(3)-η(1):η(1):η(2) coordination mode, resulting in the formation of chains along the c axis based on Cd(2)O(2) dimeric units. Adjacent chains are stacked through π-π stacking [3.533 (2) Šbetween phen and triazine rings] and C-H⋯O inter-actions, forming supra-molecular sheets in the ab plane. Intra-and intermolecular O-H⋯O hydrogen bonds are also observed.

[Prospective study of cystatin C for diagnosis of acute kidney injury after cardiac surgery].

OBJECTIVE: To prospectively study the value of cystatin C in diagnosis of acute kidney injury (AKI) in patients after cardiac surgery. METHODS: A total of 132 patients undergoing cardiopulmonary bypass were enrolled in this prospectively study. From each patient, blood samples were collected everyday before and after operation to detect the serum creatinine (Scr) and cystatin C levels by enzymatic method and particle-enhanced turbidimetric immunoassay (PETIA), respectively, and the glomerular filtration rate (eGFR) was estimated using MDRD equation. AKI diagnosis was made according to the RIFLE criteria of the Acute Dialysis Quality Initiative (ADQI) (R: Scr increased by > or =50%; I: Scr increased by > or =100%; F: Scr increased by > or =200%; L: Loss of kidney function; E: End-stage renal disease). Another AKI diagnostic criterion was also adopted according to the levels of cystatin C increment, namely an increase by > or =50%, > or =100%, and > or =200%. RESULTS: Twenty-nine patients (21.9%) developed AKI of varied severities, including 10 meeting the R-criteria, 12 the I-criteria, 7 the F-criteria, with the other 103 patients without AKI serving as the control group. Cystatin C of the 29 AKI patients was drastically increased in comparison with that of the control group (P<0.001). Significant linear correlation was found between cystatin C and Scr (r=0.732, P<0.001) and between [cystatin C]-1 and estimated GFR (R=0.803, P<0.001). By the two diagnostic criteria based on cystatin C and Scr levels, respectively, the median diagnostic time of AKI was 2 days (range 1-4 days) and 3 days (range 2-5 days) for R criteria (10 patients, P=0.014), 3.5 days (range 1-6 days) and 5 days (range 2-8 days) for I criteria (12 patients, P=0.008), and 5 days (range 3-7 days) and 6.5 days (range 4-9 days) for F criteria (7 patients, P=0.02), respectively. ROC analysis confirmed excellent accuracy of cystatin C in AKI diagnosis (AUC=0.992). With the cut-off value of cystatin C increment by > or =50%, the diagnostic sensitivity and specificity of AKI was 92% and 95%, respectively. CONCLUSION: Cystatin C can serve as a good indicator for AKI diagnosis to allow earlier detection of AKI than Scr-based diagnosis in patients after cardiac surgery.